This is an application for a K01 award for Dr. Elizabeth Fair, an epidemiologist in the Division of Pulmonary and Critical Care Medicine at the University of California, San Francisco. Dr. Fair is establishing herself as an investigator in epidemiologic and cost effectiveness analyses to evaluate the feasibility, cost, and impact of new tuberculosis (TB) case detection methods in resource limited-settings with high incidences of TB and HIV and increasing threats of drug-resistant TB. This K01 award will provide Dr. Fair with the support necessary to accomplish the following goals: (1) to become expert in applying advanced analytic methods for evaluating the cost effectiveness of programmatic TB interventions;(2) to learn to apply mathematical modeling of infectious disease transmission for evaluating the impact of TB interventions;(3) to become expert in the design, enrollment, and management of a prospective cohort study in a low-resource setting;(4) to apply laboratory research techniques for TB genotyping and drug resistance testing;and (5) to develop and independent clinical research career. To achieve these goals, Dr. Fair has assembled a mentoring team comprised of a primary mentor, Dr. Philip Hopewell, an internationally recognized authority on global TB control, and 2 co-mentors: Dr. James G. Kahn, an internationally recognized expert on cost effectiveness studies, and Dr. Travis Porco, a well-published mathematical modeler and epidemiologist. Low case finding of new TB patients is a major limitation to global control of the disease, especially in high HIV-prevalence areas. Dr. Fair's research will determine whether household contact investigation in a low-income, high TB burden setting results in earlier diagnosis of TB (Aim 1). She will also assess the costs, cost-effectiveness, and impact of contact investigation under program conditions (Aim 2);and characterize the transmissibility and pathogenicity of M.tb strains from new cases found through household contact investigation (Aim 3). The research will form the basis for a future R01 grant application to address the scientific basis of TB transmission and pathogenicity, specifically of drug-resistant M.tb strains.